Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies.

BACKGROUND: Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE). METHODS: The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses. RESULTS: AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), ß-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity. CONCLUSION: The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.

Experimental and pharmacoinformatic approaches unveil the neuropharmacological and analgesic potential of chloroform fraction of Roktoshirinchi (Achyranthes ferruginea Roxb.).

ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes ferruginea (A. ferruginea) Roxb. is a common plant used in traditional medicine in Asia and Africa. It has a variety of local names, including "Gulmanci" in Nigeria, "Dangar" in Pakistan, "Thola" in Ethiopia, and "Roktoshirinchi" in Bangladesh. It is edible and has several ethnomedical uses for a wide range of illnesses, including hysteria, dropsy, constipation, piles, boils, asthma, and shigellosis. However, the neuropharmacological and analgesic potential of A. ferruginea remains uninvestigated. AIM OF THE STUDY: To assess the neuropharmacological and analgesic potential of A. ferruginea through a multifaceted approach encompassing both experimental and computational models. MATERIALS AND METHODS: Methanol was used to extract the leaves of A. ferruginea. It was then fractionated with low to high polar solvents (n-hexane, chloroform, ethyl acetate, and water) to get different fractions, including chloroform fraction (CLF). The study selected CLF at different doses and conducted advanced chemical element and proximate analyses, as well as phytochemical profiling using GC-MS. Toxicological studies were done at 300 µg per rat per day for 14 days. Cholinesterase inhibitory potential was checked using an in-vitro colorimetric assay. Acetic acid-induced writhing (AAWT) and formalin-induced licking tests (FILT) were used to assess anti-nociceptive effects. The forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM), hole board test (HBT), and light and dark box test (LDB) were among the behavioral tests used to assess depression and anxiolytic activity. Network pharmacology-based analysis was performed on selected compounds using the search tool for interacting chemicals-5 (STITCH 5), Swiss target prediction tool, and search tool for the retrieval of interacting genes and proteins (STRING) database to link their role with genes involved in neurological disorders through gene ontology and reactome analysis. RESULTS: Qualitative chemical element analysis revealed the presence of 15 elements, including Na, K, Ca, Mg, P, and Zn. The moisture content, ash value, and organic matter were found to be 11.12, 11.03, and 88.97%, respectively. GC-MS data revealed that the CLF possesses 25 phytoconstituents. Toxicological studies suggested the CLF has no effects on normal growth, hematological and biochemical parameters, or cellular organs after 14 days at 300 µg per rat. The CLF markedly reduced the activity of both acetylcholinesterase and butyrylcholinesterase (IC50: 56.22 and 13.22 µg/mL, respectively). Promising dose-dependent analgesic activity (p < 0.05) was observed in chemically-induced pain models. The TST and FST showed a dose-dependent substantial reduction in immobility time due to the CLF. Treatment with CLF notably increased the number of open arm entries and time spent in the EPM test at doses of 200 and 400 mg/kg b.w. The CLF showed significant anxiolytic activity at 200 mg/kg b.w. in the HBT test, whereas a similar activity was observed at 400 mg/kg b.w. in the EPM test. A notable increase in the amount of time spent in the light compartment was observed in the LDB test by mice treated with CLF, suggesting an anxiolytic effect. A network pharmacology study demonstrated the relationship between the phytochemicals and a number of targets, such as PPARA, PPARG, CHRM1, and HTR2, which are connected to the shown bioactivities. CONCLUSIONS: This study demonstrated the safety of A. ferruginea and its efficacy in attenuating cholinesterase inhibitory activity, central and peripheral pain, anxiety, and depression, warranting further exploration of its therapeutic potential.

Exploring the therapeutic potential of edible vegetables, fruits, and spices against cancer in various cell lines.

Cancer is rapidly becoming the leading cause of death globally. This study aimed to identify edible foods with cytotoxic and/or antioxidant activities that can prevent cancer when consumed in a regular diet. Sixty-eight edible foods were purchased from the local market, and the materials were extracted with 80% methanol. The cytotoxic activity of the extracts was evaluated using MTT on HeLa, H2228, HEK293, and H3122 cell lines. To study apoptosis, triple fluorescence labeling with DAPI, Annexin V, and propidium iodide was used. The phenolic content, antioxidant capacity, and free radical scavenging capabilities were studied using conventional spectrophotometric techniques. Among the edible foods, carrot, pointed gourd, wax gourd, ficus, apple, lemon, cumin seed, and white peppercorn showed moderate cytotoxicity in HeLa cells. The growth of HeLa cells was significantly inhibited dose-dependently by tomato, banana, Indian spinach, guava, lemon peel, and coriander (IC50, 24.54, 17.89, 13.18, 9.33, 1.23, and 2.96 µg/mL, respectively). Tomato, Indian spinach, lemon peel, and coriander exerted significant dose-dependent inhibition of H2228, HEK293, and H3122 cell proliferation. The tomato, Indian spinach, lemon peel, and coriander extracts induced HeLa cell apoptosis. White peppercorn, amaranth, apple, wax gourd, cumin seed, taro, and lemon peel contained significant amounts of polyphenols and showed high antioxidant activity. White peppercorn, apple, coriander, lemon peel, and ficus significantly scavenged DPPH free radicals (IC50 values of 10.23, 12.02, 13.49, 13.8, and 14.0 µg/mL, respectively). The overall results suggest that the daily intake of these antioxidant-rich cytotoxic foods can prevent or reduce the risk of cancer.

Apoptosis-inducing anti-proliferative and quantitative phytochemical profiling with in silico study of antioxidant-rich Leea aequata L. leaves.

Natural products have been important parts of traditional medicine since ancient times, with various promising health effects. Leea aequata (L. aequata), a natural product, has been widely used for treating several diseases due to its promising pharmacological activities. Therefore, the present study aimed to explore the phytochemical profiling and molecular docking of the antioxidant-rich part of L. aequata leaves and its antiproliferative activity. L. aequata leaves were extracted with methanol, followed by fractionation with the respective solvents to obtain the petroleum ether, chloroform, ethyl acetate, and aqueous fractions. The antioxidant activity was evaluated by spectrophotometric methods. The cytotoxic and antiproliferative activities were detected using MTT colorimetric and confocal microscopy methods, respectively. Phytochemical compositions were analyzed using gas chromatography‒mass spectrometry analysis. Computer aided (molecular docking SwissADME, AdmetSAR and pass prediction) analyses were undertaken to sort out the best-fit phytochemicals present in the plant responsible for antioxidant and anticancer effects. Among the fractions, the ethyl acetate fraction was the most abundant polyphenol-rich fraction and showed the highest antioxidant, reducing power, and free radical scavenging activities. Compared to untreated MCF-7 cells, ethyl acetate fraction-treated MCF-7 cells showed an increase in apoptotic characteristics, such as membrane blebbing, chromatin condensation, and nuclear fragmentation, causing apoptosis and decreased proliferation of HeLa and MCF-7 cells. Furthermore, gas chromatography mass spectrometry data revealed that the ethyl acetate fraction contained 16 compounds, including methyl esters of long-chain fatty acids, which are the major chemical constituents. Moreover, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to have antioxidant and cytotoxic activity, as confirmed by computer-aided models. A strong correlation was observed between the antioxidant and polyphenolic contents and the anticancer activity. In conclusion, we explored the possibility that L. aequata could be a promising source of antioxidants and anticancer agents with a high phytochemical profile.

Lasia spinosa (L.) thw. attenuates chemically induced behavioral disorders in experimental and computational models.

Lasia spinosa (L.) Thw. (L. spinosa) is widely used as a folk remedy for different physical ailments, and its neurological effects have yet to be assessed. Phytochemicals status of L. spinosa was evaluated by GC-MS analysis. Membrane stabilization test, elevated plus maze (EPM) tests and hole board tests (HBT), tail suspension tests (TST) and thiopental sodium-induced sleeping tests (TISTT) were used to assess anti-inflammatory, anxiolytic and anti-depressant activity. Fourteen compounds have been recorded from GC-MS analysis. The LSCTF showed 68.66 ± 2.46% hemolysis protections (p < 0.05) at 500 µg/mL, whereas LSCHF and LSNHF demonstrated efficiency rates of 68.6 ± 1.46% and 52.46 ± 5.28%, respectively. During EPM tests, LSNHF and LSCTF significantly (p < 0.001) increased the time spent in the open arm (59.88 ± 0.65 s and 50.77 ± 0.67 s, respectively) at the dosages of 400 mg/kg. In HBT, samples exhibited dose-dependent anxiolytic activity. LSNHF and LSCTF showed a significant (p < 0.001) hole poking tendency and a high number of head dips (78.66 ± 1.05 and 65.17 ± 0.96, respectively) at the higher dose. In TST, at 400 mg/kg dose demonstrated significantly (p < 0.001) smaller amounts of time immobile, at 81.33 ± 1.67 s and 83.50 ± 1.90 s, respectively, compared to the control group. A consistent finding was also observed in TISTT. The computer-assisted studies on the identified compounds strongly support the aforementioned biological activities, indicating that L. spinosa has potential as a source of medication for treating neuropsychiatric and inflammatory diseases.

Chemical profiles and pharmacological attributes of Apis cerana indica beehives using combined experimental and computer-aided studies.

The current study sought to determine the anxiolytic, antidepressant, and anti-inflammatory properties of distilled water-soluble extract of beehive (WSE-BH). Gas chromatography-mass spectrometry (GC-MS) studies were used to characterize the chemical compositions obtained from beehives extracted in water and methanol (also fractions). The GC-MS analysis identified 19 compounds in WSE-BH, including high total phenol and flavonoid contents, compared with the methanol extract (21 compounds), ethyl acetate fraction (9 compounds), and CCl4 fraction (27 compounds). The oral administration of WSE-BH (50 and 150 mg/kg) showed significant anxiolytic activities assessed by time spent in (30.80% and 39.47%, respectively) and entry into (47.49% and 55.93%, respectively) the open arms of the elevated plus-maze (EPM). Only the 150 mg/kg dose resulted in a significant effect on the number of head-dipping events in the hole-board test (HBT) (40.2 ± 2.33; p < 0.01) vs. diazepam (64.33 ± 3.16; p < 0.001). Both the 50 and 150 mg/kg doses resulted in significant (p < 0.001) decreases in immobility in the forced swim test (FST) and tail suspensions test (TST), corresponding to the effect of fluoxetine. WSE-BH inhibited histamine-induced paw edema significantly beginning at 60 min, with the 150 mg/kg dose having the highest effect at 180 min. The current findings suggested that WSE-BH had anxiolytic, antidepressant, and anti-inflammatory properties.

Pharmacological insights into Chukrasia velutina bark: Experimental and computer-aided approaches.

BACKGROUND: Chukrasia velutina is an enthnomedicinally used plant reported to have significant medicinal values. The present study aimed to explore the pharmacological activities of bark methanol extract using in vitro, in vivo and in silico models. METHODS: The study was designed to investigate the pharmacological effects of methanol extract of Chukrasia velutina bark (MECVB) through in vitro, in vivo and in silico assays. Analgesic activity was tested using formalin-induced nociception and acetic acid-induced writhing assays while the antipyretic effect was tested using yeast-induced hyperthermia in mice model. The antioxidant effect was tested using the DPPH and reducing power assay and the cytotoxic screening was tested using the brine shrimp lethality bioassay. In addition, in silico studies were conducted using computer aided methods. RESULTS: In the acetic acid-induced writhing assay, the extract showed 28.36% and 56.16% inhibition of writhing for doses of 200 and 400 mg/kg, respectively. Moreover, a dose-dependent formalin-induced licking response was observed in both early and late phase. In yeast-induced pyrexia, the MECVB exhibited (p < 0.05) antipyretic effect. The extract demonstrated an IC50 value of 78.86 µg/ml compared with ascorbic acid (IC50 23.53 µg/ml) in the DPPH scavenging assay. The compounds sitosterol, 5,7-dimethoxycoumarin and scopoletin were seen be effective in molecular docking scores against COX-I (2OYE), COX-II (6COX) and human peroxiredoxin 5 (1HD2). In ADME/T analysis, 5,7-dimethoxycoumarin and scopoletin satisfied Lipinski's rule of five and thus are potential drug candidates. CONCLUSION: The bark of Chukrasia velutina showed significant analgesic and antipyretic properties and is a potential source of natural anti-oxidative agents.

Traditional uses, pharmacological activities, and phytochemical constituents of the genus Syzygium: A review.

The genus Syzygium comprises 1200-1800 species that belong to the family of Myrtaceae. Moreover, plants that are belonged to this genus are being used in the traditional system of medicine in Asian countries, especially in China, India, and Bangladesh. The aim of this review is to describe the scientific works and to provide organized information on the available traditional uses, phytochemical constituents, and pharmacological activities of mostly available species of the genus Syzygium in Bangladesh. The information related to genus Syzygium was analytically composed from the scientific databases, including PubMed, Google Scholar, Science Direct, Web of Science, Wiley Online Library, Springer, Research Gate link, published books, and conference proceedings. Bioactive compounds such as flavanone derivatives, ellagic acid derivatives and other polyphenolics, and terpenoids are reported from several species of the genus Syzygium. However, many members of the species of the genus Syzygium need further comprehensive studies regarding phytochemical constituents and mechanism-based pharmacological activities.

Incredible affinity of Kattosh with PPAR-γ receptors attenuates STZ-induced pancreas and kidney lesions evidenced in chemicobiological interactions.

Since ancient times, plants have been used as green bioresources to ensure a healthier life by recovering from different diseases. Kattosh (Lasia spinosa L. Thwaites) is a local plant with various traditional uses, especially for arthritis, constipation and coughs. This research investigated the effect of Kattosh stem extract (LSES) on streptozotocin-induced damage to the pancreas, kidney, and liver using in vitro, in vivo and in silico methods. In vitro phytochemical, antioxidative and anti-inflammatory effects of LSES were accomplished by established methods followed by antidiabetic actions in in vivo randomized controlled intervention in STZ-induced animal models for four weeks. In an in silico study, LSES phytocompounds interacted with antidiabetic receptors of peroxisome proliferator-activated receptor-gamma (PPAR, PDB ID: 3G9E), AMP-activated protein kinase (AMPK, PDB ID: 4CFH) and α-amylase enzyme (PDB ID: 1PPI) to verify the in vivo results. In addition, LSES showed promising in vitro antioxidative and anti-inflammatory effects. In contrast, it showed a decrease in weekly blood glucose level, normalized lipid profile, ameliorated liver and cardiac markers, managed serum AST and ALT levels, and increased glucose tolerance ability in the animal model study. Restoration of pancreatic and kidney damage was reflected by improving histopathological images. In ligand-receptor interaction, ethyl α-d-glucopyranoside of Kattosh showed the highest affinity for the α-amylase enzyme, PPAR, and AMPK receptors. Results demonstrate that the affinity of Kattosh phytocompounds potentially attenuates pancreatic and kidney lesions and could be approached as an alternative antidiabetic source with further clarification.

Chemical profiles and pharmacological insights of Anisomeles indica Kuntze: An experimental chemico-biological interaction.

Anisomeles indica (L.) Kuntze is an ethnomedicinally important plant that has long been used in traditional medicine to treat a variety of ailments, including dyspepsia, abdominal pain, colic, allergies, inflammation, and rheumatic arthritis. However, the scientific framework underlying these medicinal properties is not well known. This study aimed to investigate the antidepressive, antidiarrheal, thrombolytic, and anti-inflammatory potential of a methanol extract of A. indica (MeOH-AI). The potential bioactive compounds in the MeOH-AI were identified using gas chromatography-mass spectrometry (GC-MS), and antidepressant activities were evaluated using the tail suspension test (TST) and forced swim test (FST). Antidiarrheal effects were also assayed in castor oil-induced diarrhea and gastrointestinal motility studies. The anti-inflammatory activities were explored by examining the effects on protein inhibition and denaturation in heat- and hypotonic solution-induced hemolysis assays. The thrombolytic activity was evaluated using the clot lysis test in human blood. BIOVIA and Schrödinger Maestro (v11.1) were applied for docking analysis to determine binding interactions, and the absorption, distribution, metabolisms, excretion/toxicity (ADME/T) properties of bioactive compounds were explored using a web-based method. The GC-MS analysis of MeOH-AI revealed the presence of several bioactive compounds. MeOH-AI administration resulted in significant (p < 0.01) reductions in the immobility times for both the FST and TST compared with those in the control group. MeOH-AI also induced significant (p < 0.01) reductions in castor oil-induced diarrhea severity and gastrointestinal motility in a mouse model. In addition, the in vitro anti-inflammatory and thrombolytic activity studies produced remarkable responses. The binding assay showed that 4-dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine interacts favorably with monoamine oxidase and serotonin and M3 muscarinic acetylcholine receptors, displaying good pharmacokinetic properties, which may mediate the effects of MeOH-AI on depression and diarrhea. Overall, the research findings indicated that MeOH-AI has significant antidepressant, antidiarrheal, and anti-inflammatory effects and may represent an alternative source of novel therapeutic factors.

Antioxidative role of palm grass rhizome ameliorates anxiety and depression in experimental rodents and computer-aided model.

Palm grass (Curculigo recurvata) is an ethnomedicinally important herb reported to have significant medicinal values. The present study aimed to evaluate the antidepressant and anxiolytic activities of a methanol extract of C. recurvata rhizome (Me-RCR) through different approaches. The antidepressant and anxiolytic properties of Me-RCR were assessed by using elevated plus maze (EPM), hole-board (HBT), tail suspension (TST), and forced swimming (FST) tests in Swiss Albino mice. The in-depth antioxidative potential of Me-RCR was also evaluated through DPPH radical scavenging activity, ferric-reducing power capacity, total phenolic, flavonoid, flavonol, and antioxidant content analysis. Computational investigations were performed using computer-aided methods for screening the anxiolytic, antidepressant, and antioxidative activities of the selected lead molecules. Treatment with Me-RCR (200 and 400 mg/kg, b.w.) notably increased the number of open arm entries and the time spent in the EPM test. In the HBT, Me-RCR exhibited significant anxiolytic activity at a dose of 200 mg/kg, whereas similar activity was observed at 400 mg/kg in the EPM test. Me-RCR significantly decreased the immobility time in a dose-dependent manner in both TST and FST. The IC50 for DPPH and reducing power capacity assay were found to be 18.56 and 193 µg/mL, respectively. Promising outcomes were noted for the determination of total phenolics, flavonoids, flavonols, and antioxidant capacity. In the case of computer-aided studies, nyasicoside showed promising binding energy for antidepressant and anxiolytic activities, whereas isocurculigine demonstrated promising effects as an antioxidant. Overall, these findings suggest that Me-RCR could be a favourable therapeutic candidate for the treatment of mental and psychiatric disorders, as well as a good source of antioxidants.

Epiphytic Acampe ochracea orchid relieves paracetamol-induced hepatotoxicity by inhibiting oxidative stress and upregulating antioxidant genes in in vivo and virtual screening.

Orchids are basically ornamental, and biological functions are seldom evaluated. This research investigated the effects of Acampe ochracea methanol extract (AOME) in ameliorating the paracetamol (PCM) induced liver injury in Wistar albino rats, evaluating its phytochemical status through UPLC-qTOF-MS analysis. With molecular docking and network pharmacology, virtual screening verified the inevitable interactions between the UPLC-qTOF-MS-characterized compounds and hepatoprotective drug receptors. The AOME has explicit a dose-dependent decrease of liver enzymes acid phosphatase (ACP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin, as well as an increase of serum total protein and antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH) with a virtual normalization (p < 0.05-p < 0.001) and the values were almost equivalent to the reference drug silymarin. After pretreatment with AOME, PCM-induced malondialdehyde (MDA) levels were considerably decreased (p < 0.001). Histopathological examinations corroborated the functional and biochemical findings. The AOME upregulated the genes involved in antioxidative (CAT, SOD, ß-actin, PON1, and PFK1) and hepatoprotective mechanisms in PCM intoxicated rats. An array of 103 compounds has been identified from AOME through UPLC-qTOF-MS analysis. The detected compounds were substantially related to the targets of several liver proteins and antioxidative enzymes, according to an in silico study. Virtual prediction by SwissADME and admetSAR showed that AOME has drug-like, non-toxic, and potential pharmacological activities in hepatic damage. Furthermore, VEGFA, CYP19A1, MAPK14, ESR1, and PPARG genes interact with target compounds impacting the significant biological actions to recover PCM-induced liver damage.

Antiproliferative and antioxidant potentials of bioactive edible vegetable fraction of Achyranthes ferruginea Roxb. in cancer cell line.

In the present study, the aerial parts of Achyranthes ferruginea underwent investigation of their in vitro antioxidant and free radical-scavenging activities in cell-free conditions, their phytoconstituents using gas chromatography-mass spectrometry (GC-MS), and their cytotoxic activity in HeLa cells. A. ferruginea was extracted with 80% methanol and successively fractionated with solvents to yield petroleum ether (PEF), chloroform (CHF), ethyl acetate (EAF), and aqueous (AQF) fractions. GC-MS analysis revealed that CHF contained ten phytoconstituents, including different forms of octadecanoic acid methyl esters. The total antioxidant and ferric-reducing antioxidant capacities of the extracts and the standard catechin (CA) were as follows: CA >CHF >PEF >CME (crude methanolic extract) >EAF >AQF, and CA >CHF >EAF >PEF >AQF >CME, respectively. CHF showed the highest DPPH-free radical-scavenging activity, with a median inhibitory concentration of 10.5 ± 0.28 µg/ml, which was slightly higher than that of the standard butylated hydroxytoluene (12.0 ± 0.09 µg/ml). In the hydroxyl radical-scavenging assay, CHF showed identical scavenging activity (9.25 ± 0.73 µg/ml) when compared to CA (10.50 ± 1.06 µg/ml). Moreover, CHF showed strong cytotoxic activity (19.95 ± 1.18 µg/ml) in HeLa cells, which was alike to that of the standards vincristine sulfate and 5-fluorouracil (15.84 ± 1.64 µg/ml and 12.59 ± 1.75 µg/ml, respectively). The in silico study revealed that identified compounds were significantly linked to the targets of various cancer cells and oxidative enzymes. However, online prediction by SwissADME, admetSAR, and PASS showed that it has drug-like, nontoxic, and potential pharmacological actions.

Unfolding the apoptotic mechanism of antioxidant enriched-leaves of Tabebuia pallida (lindl.) miers in EAC cells and mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia pallida (Lindl.) Miers (T. pallida) is a well-known native Caribbean medicinal plant. The leaves and barks of T. pallida are used as traditional medicine in the form of herbal or medicinal tea to manage cancer, fever, and pain. Moreover, extracts from the leaves of T. pallida showed anticancer activity. However, the chemical profile and mechanism of anticancer activity of T. pallida leaves (TPL), stem bark (TPSB), root bark (TPRB) and flowers (TPF) remain unexplored. AIM OF THE STUDY: The present study was designed to explore the regulation of apoptosis by T. pallida using Ehrlich Ascites Carcinoma (EAC) cultured cells and an EAC mouse model. LC-ESI-MS/MS was used for compositional analysis of T. pallida extracts. MATERIALS AND METHODS: Dried and powdered TPL, TPSB, TPRB and TPF were extracted with 80% methanol. Using cultured EAC cells and EAC-bearing mice with and without these extracts, anticancer activities were studied by assessing cytotoxicity and tumor cell growth inhibition, changes in life span of mice, and hematological and biochemical parameters. Apoptosis was analyzed by microscopy and expression of selected apoptosis-related genes (Bcl-2, Bcl-xL, NFκ-B, PARP-1, p53, Bax, caspase-3 and -8) using RT-PCR. LC-ESI-MS analysis was performed to identify the major compounds from active extracts. Computer aided analyses was undertaken to sort out the best-fit phytoconstituent of total ten isolated compounds of this plant for antioxidant and anticancer activity. RESULTS: In EAC mice compared with untreated controls, the TPL extract exhibited the highest cancer cell toxicity with significant tumor cell growth inhibition (p < 0.001), reduced ascites by body weight (p < 0.01), increased the life span (p < 0.001), normalized blood parameters (RBC/WBC counts), and increased the levels of superoxide dismutase and catalase. TPL-treated EAC cells showed increased apoptotic characteristics of membrane blebbing, chromatin condensation and nuclear fragmentation, and caspase-3 activation, compared with untreated EAC cells. Moreover, annexin V-FITC and propidium iodide signals were greatly enhanced in response to TPL treatment, indicating apoptosis induction. Pro- and anti-apoptotic signaling after TPL treatment demonstrated up-regulated p53, Bax and PARP-1, and down-regulated NFκ-B, Bcl-2 and Bcl-xL expression, suggesting that TPL shifts the balance of pro- and anti-apoptotic genes towards cell death. LC-ESI-MS data of TPL showed a mixture of glycosides, lapachol, and quercetin antioxidant and its derivatives that were significantly linked to cancer cell targets. The compound, pelargonidin-3-O-glucoside was found to be most effective in computer aided models. CONCLUSIONS: In conclusion, the TPL extract of T. pallida possesses significant anticancer activity. The tumor suppressive mechanism is due to apoptosis induced by activation of antioxidant enzymes and caspases and mediated by a change in the balance of pro- and anti-apoptotic genes that promotes cell death.

Ethnomedicinal Value of Antidiabetic Plants in Bangladesh: A Comprehensive Review.

The use of conventional drugs to treat metabolic disorders and the pathological consequences of diabetes further increases the complications because of the side effects, and is sometimes burdensome due to relatively higher costs and occasionally painful route of administration of these drugs. Therefore, shifting to herbal medicine may be more effective, economical, have fewer side effects and might have minimal toxicity. The present review amasses a list of ethnomedicinal plants of 143 species belonging to 61 families, from distinctive domestic survey literature, reported to have been used to treat diabetes by the ethnic and local people of Bangladesh. Leaves of the medicinal plants were found leading in terms of their use, followed by fruits, whole plants, roots, seeds, bark, stems, flowers, and rhizomes. This review provides starting information leading to the search for and use of indigenous botanical resources to discover bioactive compounds for novel hypoglycemic drug development.

Tendencies and attitudes towards dietary supplements use among undergraduate female students in Bangladesh.

BACKGROUND: Dietary supplements (DS) are products that improve the overall health and well-being of individuals and reduce the risk of disease. Evidence indicates a rising prevalence of the use of these products worldwide especially among the age group 18-23 years. AIM: The study investigates the tendencies and attitudes of Bangladeshi undergraduate female students towards dietary supplements (DS). METHODS: A three-month (March 2018-May 2018) cross-sectional face-to-face survey was conducted in undergraduate female students in Chittagong, Bangladesh using a pre-validated dietary supplement questionnaire. The study was carried among the four private and three public university students of different disciplines in Chittagong to record their prevalent opinions and attitudes toward using DS. The results were documented and analyzed by SPSS version 22.0. RESULTS: Ninety two percent (N = 925, 92.0%) of the respondents answered the survey questions. The prevalence of DS use was high in undergraduate female students. The respondents cited general health and well-being (n = 102, 11.0%) and physician recommendation (n = 101, 10.9%) as a reason for DS use. Majority of the students (n = 817, 88.3%) used DS cost monthly between USD 0.12 and USD 5.90. Most of the students (n = 749, 81.0%) agreed on the beneficial effect of DS and a significant portion (n = 493, 53.3%) recommended for a regular use of DS. Highly prevalent use of dietary supplements appeared in Chittagonian undergraduate female students. They were tremendously positive in using DS. The results demonstrate an increasing trend of using DS by the undergraduate females for both nutritional improvement and amelioration from diseases. CONCLUSION: Dietary supplements prevalence was so much higher in students of private universities as compared to students of public universities. Likewise, maximal prevalence is indicated in pharmacy department compared to other departments. Students preferred brand products, had positive opinions and attitudes towards dietary supplements.

Therapeutic Potentials of Syzygium fruticosum Fruit (Seed) Reflected into an Array of Pharmacological Assays and Prospective Receptors-Mediated Pathways.

Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the S. fruticosum seed's fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro, and in silico studies. The SF was fractionated with different solvents, and the ethyl acetate fraction of SF (EaF-SF) was further studied. Mice treated with EaF-SF (200 and 400 mg/kg) manifested anxiolysis evidenced by higher exploration in elevated plus maze and hole board tests. Similarly, a dose-dependent drop of immobility time in a forced swimming test ensured significant anti-depressant activity. Moreover, higher dose treatment exposed reduced exploratory behaviour resembling decreased movement and prolonged sleeping latency with a quick onset of sleep during the open field and thiopental-induced sleeping tests, respectively. In parallel, EaF-SF significantly (p < 0.001) and dose-dependently suppressed acetic acid and formalin-induced pain in mice. Also, a noteworthy anti-inflammatory activity and a substantial (p < 0.01) clot lysis activity (thrombolytic) was observed. Gas chromatography-mass spectrometry (GC-MS) analysis resulted in 49 bioactive compounds. Among them, 12 bioactive compounds with Lipinski's rule and safety confirmation showed strong binding affinity (molecular docking) against the receptors of each model used. To conclude, the S. fruticosum seed is a prospective source of health-promoting effects that can be an excellent candidate for preventing degenerative diseases.

Pretreatment of Blumea lacera leaves ameliorate acute ulcer and oxidative stress in ethanol-induced Long-Evan rat: A combined experimental and chemico-biological interaction.

Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p < 0.001) inhibited gastric lesions and malondealdehyde (MDA) levels and upregulated antioxidant enzymes level. Furthermore, nine compounds were documented as bioactive, displayed good binding affinities to against gastric H+-K+ATPase enzyme while these compounds illustrated inhibitory effect. From these studies, it is established MEBLL has ulcer healing property as unveiled by in vivo and in silico studies.

Drug Repurposing Approach against Novel Coronavirus Disease (COVID-19) through Virtual Screening Targeting SARS-CoV-2 Main Protease.

Novel coronavirus disease (COVID-19) was identified from China in December 2019 and spread rapidly through human-to-human transmission, affecting so many people worldwide. Until now, there has been no specific treatment against the disease and repurposing of the drug. Our investigation aimed to screen potential inhibitors against coronavirus for the repurposing of drugs. Our study analyzed sequence comparison among SARS-CoV, SARS-CoV-2, and MERS-CoV to determine the identity matrix using discovery studio. SARS-CoV-2 Mpro was targeted to generate an E-pharmacophore hypothesis to screen drugs from the DrugBank database having similar features. Promising drugs were used for docking-based virtual screening at several precisions. Best hits from virtual screening were subjected to MM/GBSA analysis to evaluate binding free energy, followed by the analysis of binding interactions. Furthermore, the molecular dynamics simulation approaches were carried out to assess the docked complex's conformational stability. A total of 33 drug classes were found from virtual screening based on their docking scores. Among them, seven potential drugs with several anticancer, antibiotic, and immunometabolic categories were screened and showed promising MM/GBSA scores. During interaction analysis, these drugs exhibited different types of hydrogen and hydrophobic interactions with amino acid residue. Besides, 17 experimental drugs selected from virtual screening might be crucial for drug discovery against COVID-19. The RMSD, RMSF, SASA, Rg, and MM/PBSA descriptors from molecular dynamics simulation confirmed the complex's firm nature. Seven promising drugs for repurposing against SARS-CoV-2 main protease (Mpro), namely sapanisertib, ornidazole, napabucasin, lenalidomide, daniquidone, indoximod, and salicylamide, could be vital for the treatment of COVID-19. However, extensive in vivo and in vitro studies are required to evaluate the mentioned drug's activity.

Pleurotus highking mushrooms potentiate antiproliferative and antimigratory activity against triple-negative breast cancer cells by suppressing Akt signaling.

In this study, we evaluated the antiproliferative and antimetastatic effects of the Pleurotus highking mushroom on the human triple-negative breast cancer cell lines MDA-MB-231 and HCC-1937 and attempted to elucidate the underlying molecular mechanisms. The antiproliferative effects of P. highking purified fraction-III (PEF-III) were investigated using colony formation and MTS assays. The antimigratory effects of PEF-III were determined by wound healing, transwell migration, and matrigel cell invasion assays. The protein expression levels were evaluated using Western blot analysis. The effect of PEF-III on tumor-sphere formation was examined in a 3D sphere-forming medium, and the mRNA expressions of proliferation- and migration-related genes in the cells from the tumor spheres were determined using RT-qPCR. PEF-III treatment caused a potent and concentration-dependent decrease in the numbers of colonies and viable cells. It also remarkably suppressed the migratory ability of the cells. Mechanistically, PEF-III treatment reduced the expression of pAkt, matrix metallopeptidase-9 (MMP-9), and vimentin. Furthermore, PEF-III reduced the number and size of the tumor spheres in the 3D culture system. It also significantly reduced the mRNA expression of Ki-67, MMP-9, and vimentin in the PEF-III-treated tumor-sphere cells. PEF-III exerted promising antiproliferative and antimigratory effects in triple-negative breast cancer cell lines by suppressing Akt signaling. Therefore, P. highking mushrooms may be considered a potential source for the development of potent anticancer drug(s) for the treatment of breast cancer.